When analyzed in the dry, powdered form, most of the hundreds of modern synthetic organic pig-ments that have been introduced throughout the 20th century can be effectively characterized by direct temperature-resolved mass spectrometry (DTMS) [S.Q. Lomax, M. Schilling, T. Learner, in: T. Learner, P. Smithen, J.W. Krueger, M. Schilling (Eds.), Modern Paints Uncovered, Getty Conservation Institute, Tate Modern, London, 2007, p. 105]. However, their detection in paint formulations is often far more difficult, as these pigments are usually present in only very low concentrations, due to their relatively high tint-ing strengths. The situation is also more complex when one attempts to identify these pigments from microscopic samples of paint taken from actual works of art, due to the frequent manipulation, mixing, or adulteration of paints by artists during their application. A project aiming to characterize the wide range of pigments found in the paints of Sam Francis (American, 1923-1994) prompted work to investi-gate more fully the sensitivity of a DTMS system by comparing various ionization conditions, including electron impact (EI) at 70 and 16 eV, and chemical ionization (CI) with iso-butane in both positive- and negative-ion modes. Overall, it was found that negative-ion CI conditions showed the best results for detecting the majority of synthetic organic pigments tested: the very limited fragmentation it produced in most of the pigments resulted in a much stronger and more readily detectable molecular ion that could be more easily distinguished from the lower m/z-value ions typically coming from other components in the paints.